The present invention relates to a series of new carbacyclin derivatives and describes processes for their preparation and compositions containing them.
The compound known by the trivial name "carbacyclin" is described, for example, in United Kingdom Patent Specification No. 2,012,265, which describes and claims a series of compounds which may be represented by the general formula: ##STR2## and various salts and esters thereof. Carbacyclin is one of the isomers of the compound having this formula in which r is 4 and R.sup.a represents a pentyl group. The compounds of United Kingdom Patent Specification No. 2,012,265 have strong platelet aggregation inhibitory activity, comparable with that of the known prostaglandin E.sub.1, but are much more stable than prostaglandin E.sub.1.
Another related compound has been briefly described in a lecture entitled "Preparation of new prostacyclin-carbon analogs" by Y. Torizawa, M. Shibazaki and S. Ikegami and reported as an abstract in the reports of The 103.sup.rd Annual Meeting of the Pharmaceutical Society of Japan, April 1983, page 156. The relevant compound has the formula: ##STR3## and a method of producing this compound is described. The compound is said to have biological activity, although the nature of this activity is not defined in the published abstract. We have shown that the compound has the ability to inhibit aggregation blood platelets.
We have now discovered a series of novel carbacyclin derivatives which surprisingly have an ability to inhibit the aggregation of blood platelets which is significantly better than that of certain well-known compounds, for example, prostaglandin E.sub.1 and the prostacyclin derivatives of United Kingdom Patent Specification No. 2,012,265 (including carbacyclin), and which is also better than that of the compound disclosed in the aforementioned lecture. Moreover, the activity of the compounds in vivo is of much greater duration, which means that the compounds can be given less frequently and/or in lower doses.